Recent FDA-approval of topotecan (9-dimethylaminomethyl-10hydroxycamptohecin) and camptosar (CPT-11) along with accelerated clinical development of related camptothecin drugs provides new hope for the successful treatment of human cancer, including neoplasms for which no effective treatment currently exist. One approved use of topotecan is for treatment of ovarian cancer. However, topotecan has a narrow therapeutic range. To this end, technological advances, which provide a direct and rapid means of measuring plasma drug levels would be of great utility. We performed direct fluorescence studies of topotecan and SN-38 in human plasma and topotecan in whole blood at micromolar level using two-photon excitation at 730 and 820 nm. Since skin, blood and other tissues are translucent at long wavelength, our results suggest the attractive possibility of homogenous or noninvasive clinical sensing of camptothecins in situ using two-photon excitation.